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Switch-on effect on conformation-specific arylamine-DNA adduct by cyclometalated Ir(III) complexes

David Dayanidhi Paul Elisa1,2, Vaidyanathan Vaidyanathan Ganesan3,4

  • 1Advanced Materials Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600 020, India.

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
|February 14, 2020
PubMed

Insights

Two novel iridium(III) complexes detect specific DNA adduct conformations. These probes offer a switch-on luminescence for identifying arylamine-DNA adducts and their mutations.

Area of Science:

  • Coordination Chemistry
  • Chemical Biology
  • Molecular Recognition

Background:

  • Arylamines form covalent DNA adducts upon metabolic activation, leading to mutations.
  • These adducts adopt various conformations (B, S, W) influenced by flanking DNA bases.
  • Detecting these conformational differences is crucial but challenging.

Purpose of the Study:

  • To develop novel iridium(III) complexes as probes for detecting DNA adduct conformations.
  • To investigate the interaction of these complexes with N-acetyl-2-aminofluorene-dG (AAF-dG) adducts.
  • To determine the sequence selectivity and binding mode of the iridium(III) complexes.

Main Methods:

  • Synthesis of two iridium(III)-based cyclometalated complexes: [Ir(ppy)2(imiphen)]+ (1) and [Ir(ppy)2(furphen)]+ (2).
  • Luminescence and quenching studies using modified DNA sequences (NarI sequence with AAF-dG adducts).
  • Analysis of binding specificity towards different adduct positions (G1, G2, G3) and flanking bases (C, T).

Main Results:

  • Both iridium(III) complexes exhibit high specificity for binding to AAF-dG adducts at G1 and G3 positions.
  • Binding selectivity is influenced by the next flanking base: cytosine favors G3AAF, while thymine favors G1AAF for complex 1 (and vice versa for complex 2).
  • Quenching studies confirm that the complexes bind to AAF-dG sequences via the minor groove.

Conclusions:

  • The developed iridium(III) complexes act as effective luminescent probes for distinguishing DNA adduct conformations.
  • The observed 'switch-on' luminescence provides a method for detecting conformational heterogeneity in DNA adducts.
  • This approach holds potential for the early detection of various covalent-DNA adducts and associated mutations.
Keywords:
Arylamine-DNAConformationConformational heterogeneityIridium(III)NarI sequence

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